This laboratory is engaged in studies on protein structure and the mechanism of protein folding. The main subject of research is swine pepsinogen, a monomeric protein of molecular weight = 39,630, which is stable at pH's between 6 and 8.5. Below pH 6 pepsinogen activates itself by proteolytic loss of it's first 44 amino acids, to produce an enzymatically active protein, pepsin. Pepsin is stable only at pH's below 6. Pepsin and pepsinogen are unfolded by exposure to high pH, temperature or concentrations of denaturants, such as urea. However, unfolded pepsinogen can refold to its normal structure, when returned to native conditions, whereas pepsin cannot. I am interested in the mechanism of this refolding reaction and how the difference in sequence influences the refolding of the two proteins. We have used rapid kinetic techniques, (stopped-flow and T-jump), to detect partly folded intermediate forms in the folding reaction; their structures have been partially determined and the nature of the chemical reactions which separate them from the native and unfolded forms investigated. Techniques such as ultra-violet absorbance, circular dichroic and fluorescence spectroscopies, together with chemical modification and peptide chemistry, to characterize the structures of native and unfolded forms of these and other proteins, including tryptophan synthase, human nuclear thyroid hormone receptor and sulphotransferase enzymes.